PT - JOURNAL ARTICLE AU - Dominik Wiemuth AU - Stefan Grunder TI - The Pharmacological Profile of Brain Liver Intestine na+ Channel (BLINAC): Inhibition by Diarylamidines and Activation by Fenamates AID - 10.1124/mol.111.073726 DP - 2011 Jan 01 TA - Molecular Pharmacology PG - mol.111.073726 4099 - http://molpharm.aspetjournals.org/content/early/2011/08/09/mol.111.073726.short 4100 - http://molpharm.aspetjournals.org/content/early/2011/08/09/mol.111.073726.full AB - The ion channel BLINaC (Brain Liver Intestine Na+ Channel) is a member of the DEG/ENaC gene family of unknown function. Elucidation of the physiological function of BLINaC would greatly benefit from pharmacological tools that specifically affect BLINaC activity. Guided by the close molecular relation of BLINaC to acid sensing ion channels (ASICs), we discovered in this study that rBLINaC and mBLINaC are inhibited by micromolar concentrations of diarylamidines and nafamostat, similar to ASICs. Inhibition was voltage-dependent, suggesting pore block as the mechanism of inhibition. Furthermore we identified the fenamate flufenamic acid (FFA) and related compounds as agonists of rBLINaC. Application of millimolar concentrations of FFA to rBLINaC induced a robust, Na+-selective current, which was partially blocked by amiloride. The identification of an artificial agonist of rBLINaC supports the hypothesis that rBLINaC is opened by an unknown physiological ligand. Inhibition by diarylamidines and activation by fenamates defines a unique pharmacological profile for BLINaC, which will be useful to unravel the physiological function of this ion channel.